This study will assess the efficacy and safety of secukinumab in patients with active ankylosing spondylitis who are intolerant to or have had an inadequate response to NSAIDs, DMARDs and / or TNFα inhibitor therapy.

A Randomized, Double-blind, Placebo-controlled, Multicenter Study of Secukinumab to Demonstrate the 16 Week Efficacy and to Assess the Long Term Safety, Tolerability and Efficacy up to 2 Years in Patients With Active Ankylosing Spondylitis

ASAS 20 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 3 of a conventional set of 4 clinical domains relevent to AS and no worsening in the fourth domain. ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.

ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 40% improvement in score in at least 3 of a conventional set of 4 clinical domains relevent to AS and no worsening in the fourth domain. ASAS 40 is used to assess the efficacy of at least one dose of secukinumab against placebo.

Blood levels of C-reactive protein (CRO), an acute phase reactant, are indicative of inflammation and of its severity, and can be used to monitor treatment response. A high sensitvity CRP (hsCRP) test is implemented in this study to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over time.

ASAS 5/6 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevent to AS and no worsening in the remaining domain. In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab against placebo.

BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, the BASDAI is used to assess the efficacy of at least one dose of secukinumab verus placebo.

SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both phyically and emotionally based. Two overall summary scores, the Phyical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.

ASQoL is an 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a participant with AS: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). In this study, ASQoL is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.

ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale of 10. In this study ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.

These assessments will be implemented in terms of physical examination and vital signs outcomes, clinical laboratory results, nature and frequency of the observed adverse events and serious adverse events, frequency and severity of any injection site reactions, ECG outcomes and the detection of immunogencity. During the first 16 weeks of the study, comparisons between the secukinumab treatment arms and the placebo treatment arm will also take place.

Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.

Drug: Secukinumab (75 mg)

Secukinumab (75 mg)

Experimental: Secukinumab 10 mg/kg i.v. / 150 mg s.c.

Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.

Drug: Secukinumab (150 mg)

Secukinumab (150 mg)

Placebo Comparator: Placebo

Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.

Drug: Placebo

Placebo

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion criteria:

Male or non-pregnant, non-lactating female patients at least 18 years of age

Diagnosis of moderate to severe AS with prior documented radiologic evidence (X-ray) fulfilling the Modified New York criteria for AS (1984)

Patients should have been on NSAIDs with an inadequate response

Patients who are regularly taking NSAIDs as part of their AS therapy are required to be on a stable dose

Patients who have been on an anti-TNFα agent (not more than one) must have experienced an inadequate response

Exclusion criteria:

Chest X-ray with evidence of ongoing infectious or malignant process

Patients with total ankylosis of the spine

Patients previously treated with any biological immunomodulating agents except for those targeting TNFα

Previous treatment with any cell-depleting therapies

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358175